Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice.

Abstract

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE-/-) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE-/- mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractional shortening and ejection fraction compared with e-cigarette (0%) and saline. Ventricular transcriptomic analysis revealed changes in genes associated with metabolism, circadian rhythm, and inflammation in e-cigarette (2.4%)-treated ApoE-/- mice. Transmission electron microscopy revealed that cardiomyocytes of mice treated with e-cigarette (2.4%) exhibited ultrastructural abnormalities indicative of cardiomyopathy. Additionally, we observed increased oxidative stress and mitochondrial DNA mutations in mice treated with e-cigarette (2.4%). ApoE-/- mice on e-cigarette (2.4%) had also increased atherosclerotic lesions compared with saline aerosol-treated mice. These results demonstrate adverse effects of e-cigarettes on cardiac function in mice.NEW & NOTEWORTHY The present study is the first to show that mice exposed to nicotine electronic cigarettes (e-cigarettes) have decreased cardiac fractional shortening and ejection fraction in comparison with controls. RNA-seq analysis reveals a proinflammatory phenotype induced by e-cigarettes with nicotine. We also found increased atherosclerosis in the aortic root of mice treated with e-cigarettes with nicotine. Our results show that e-cigarettes with nicotine lead to detrimental effects on the heart that should serve as a warning to e-cigarette users and agencies that regulate them.

• Authors: Jorge Espinoza-Derout, Kamrul M Hasan, Xuesi M Shao, Maria C Jordan, Carl Sims, Desean L Lee, Satyesh Sinha, Zena Simmons, Norma Mtume, Yanjun Liu, Kenneth P Roos, Amiya P Sinha-Hikim, Theodore C Friedman
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 317 Issue 2 Pg. H445-H459 (08 01 2019) ISSN: 1522-1539 [Electronic] United States
• PMID: 31172811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial
• Nicotinic Agonists
• Reactive Oxygen Species
• Nicotine

Topics

• Animals
• Atherosclerosis (etiology, genetics, metabolism, pathology)
• DNA, Mitochondrial (genetics, metabolism)
• Disease Models, Animal
• Electronic Nicotine Delivery Systems
• Inhalation Exposure (adverse effects)
• Male
• Mice, Inbred C57BL
• Mice, Knockout, ApoE
• Mutation
• Myocytes, Cardiac (metabolism, ultrastructure)
• Nicotine (toxicity)
• Nicotinic Agonists (toxicity)
• Oxidative Stress
• Plaque, Atherosclerotic
• Reactive Oxygen Species (metabolism)
• Stroke Volume
• Transcriptome
• Vaping (adverse effects)
• Ventricular Dysfunction, Left (etiology, genetics, metabolism, physiopathology)
• Ventricular Function, Left